The objective of this research proposal is to define the importance of activation of the alternate pathway (A.P.) of complement in disease. We will determine the incidence of A.P. activation in certain autoimmune diseases in idiopathic urticaria and in bronchial asthma. We will attempt to isolate activators in the sera of such patients, characterize them and study mechanisms of activation. A strain of C4 deficient rats will also be used to clarify the necessity or otherwise of an intact C142 reaction for activation of the A.P. Since both pathways induce tissue damage by C3-9 reactions, work initiated previously on the C5-7 trimolecular complex will be extended, particularly to study properties of this high molecular weight chemotactic factor and to clarify the mechanism by which lipopolysaccharide (endotoxin) is inactivated by C5-7. The methodology in these studies would involve the use of isolated complement components in highly purified form and specific antibodies to these components. Complement proteins will be quantitated by hemolytic assays as well as immunodiffusion techniques. Activation of A.P. will be assayed by using glutahione-treated red cells and by detecting conversion products of C3, C3PA and properdin.